The research proposed in this renewal application is a continuation of originally proposed research which is an attempt to examine the composition of the extracellular fluid compartment of the brain to determine which, if any, biogenic amines are involved in the behavioral action of drugs of abuse. Operant conditioning techniques are employed to study the dependent behavioral variables because it offers a good control for determining if brain perfusion itself affects CNS function and because the experimenter can objectively and automatically control and analyze behavior. This proposal will also test several hypotheses regarding the reinforcing consequence of behavior engendered by the withdrawal state and determine if acute stimulant administration to opiate dependent rats has a differential effect upon animals who are dominant versus animals who are submissive members of a paired social hierarchy. The involvement of various monoamine transmitters and Ca ions in behavioral consequences of amphetamine, cocaine and/or opiate withdrawal will be examined. The involvement of prostaglandins E and F in the mediation of the behavioral actions of morphine and amphetamines and the development of tolerance to and dependence upon these agents will be examined. BIBLIOGRAPHIC REFERENCES: C.R. Chapman and S.B. Sparber, Prevention or reversal of operant behavioral disruption during precipitated withdrawal by treatment with morphine before or after naloxone. (Abstract) Federation Proceedings 35(3):265, 1976. J.A. Nielsen and S.B. Sparber, Intraventricularly perfused prostaglandin F2 alpha and dopamine metabolites, fixed ratio behavior and rectal temperature. (Abstract) Pharmacologist, Fall (1976).